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Hexamethylphosphoramide and hexamethylmelamine are effective as male house fly chemosterilants. Both compounds are structurally similar to the two highly active sterilants tepa and tretamine, but they differ from the aziridinyl compounds in their low toxicity for mammals and in their lack of alkylating properties. This discovery of nonalkylating male sterilants of low toxicity should substantially increase the scope and practicality of the sterilemale control method.

Provides a brief review of the use of pheromones and other behavior-controlling chemicals in pest control. Topics include control of moths, butterflies, beetles, aphids, nematodes, and slugs. (BB)

Presents a brief review of pesticide use. Included topics are: biological activity, formulation, application, uptake, metabolism, residues, and tolerance. (BB)

Describes a high school chemistry student's research project in which limonene was isolated from the oil of lemons and oranges. Outlines the students' tests on the use of this chemical as an insecticide. Discusses possible extensions of the exercises based on questions generated by the students. (TW)

The versatility of cytochrome P450 reductase (CPR) in transferring electrons to P450s from other closely related species has been extensively exploited, e.g., by using An. gambiae CPR (AgCPR), as a homologous surrogate, to validate the role of An. funestus P450s in insecticide resistance. However, genomic variation between the AgCPR and An. funestus CPR (AfCPR) suggests that the full metabolism spectrum of An. funestus P450s might be missed when using AgCPR. To test this hypothesis, we expressed AgCPR and AfCPR side-by-side with CYP6P9a and CYP6P9b and functionally validated their role in the detoxification of insecticides from five different classes. Major variations were observed within the FAD- and NADP-binding domains of AgCPR and AfCPR, e.g., the coordinates of the second FAD stacking residue AfCPR-Y456 differ from that of AgCPR-His456. While no significant differences were observed in the cytochrome c reductase activities, when co-expressed with their endogenous AfCPR, the P450s significantly metabolized higher amounts of permethrin and deltamethrin, with CYP6P9b-AfCPR membrane metabolizing α-cypermethrin as well. Only the CYP6P9a-AfCPR membrane significantly metabolized DDT (producing dicofol), bendiocarb, clothianidin, and chlorfenapyr (bioactivation into tralopyril). This demonstrates the broad substrate specificity of An. funestus CYP6P9a/-b, capturing their role in conferring cross-resistance towards unrelated insecticide classes, which can complicate resistance management.

The effect of pesticides on insects is often discussed in terms of acute and chronic toxicity, but an important and often overlooked aspect is the impact of sublethal doses on insect physiology and behavior. Pesticides can influence various physiological parameters of insects, including the innate immune system, development, and reproduction, through a combination of direct effects on specific exposed tissues and the modification of behaviors that contribute to health and reproductive success. Such behaviors include mobility, feeding, oviposition, navigation, and the ability to detect pheromones. Pesticides also have a profound effect on insect learning and memory. The precise effects depend on many different factors, including the insect species, age, sex, caste, physiological condition, as well as the type and concentration of the active ingredients and the exposure route. More studies are needed to assess the effects of different active ingredients (and combinations thereof) on a wider range of species to understand how sublethal doses of pesticides can contribute to insect decline. This review reflects our current knowledge about sublethal effects of pesticides on insects and advancements in the development of innovative methods to detect them.

In this work, magnetic graphene oxide nanoparticles were successfully synthesized by a mechanochemical approach and used as an effective sorbent in magnetic dispersive solid phase extraction of insecticides from vegetable samples followed by high-performance liquid chromatography coupled with UV-Vis detection. Imidacloprid (IMI) and chlorpyrifos (CP) were selected as model insecticides to validate the extraction performance of the obtained nanoparticles. The synthesized magnetic graphene oxide nanoparticles were characterized. Various factors which could affect the recovery were investigated and optimized. Under the optimum conditions, the calibration curves were linear in the ranges of 0.002-5 and 0.004-10 [micro]g/mL for IMI and CP, respectively. Also, the limits of detection for IMI and CP were 1.5 and 4 [mu]g/L, and the limits of quantitation were 5 and 11 [mu]g/L, respectively. The linearity (R > 0.999) and precision (between 3.3 and 6.7%) were good. Notably, the developed method could be used to determine and monitor IMI and CP residues in Chinese cabbage, shiitake, and needle mushroom samples with satisfactory recoveries., Author(s): Ou Sha [sup.1], Jiawei Yao [sup.2], Yuqing Zhu [sup.2], Hua Liu [sup.1], Quan Zhou [sup.2], Li Chen [sup.3] Author Affiliations: (1) School of Environment and Chemical Engineering, Jiangsu Ocean [...]

Insecticides not only control target pests but also adversely affect non-target communities including humans, animals, and microbial communities in host plants and soils. The effect of insecticides on non-target communities, especially endophytic bacterial communities, remains poorly understood. Two phases of treatments were conducted to compare the trends in endophytic bacterial response after insecticide application. Endophytic bacteria were isolated at 2 and 4 weeks after germination. Most insecticide treatments showed a declining trend in bacterial diversity and abundance, whereas an increasing trend was observed in the control. Therefore, insecticide use negatively affected non-target endophytic bacterial communities. Bacillus spp. was mostly dominant in the early stage in both insecticide treatment and control groups. Nevertheless, in the matured stage, mostly bacteria including Pseudomonas spp., Priestia spp. were dominant in groups treated with high insecticide concentrations. Therefore, plants can regulate and moderate their microbiome during their lifecycle depending on surrounding environmental conditions.

The use of pesticides is unavoidable in agricultural practices. This class of chemicals is highly toxic for the environment as well as for humans. The present work was carried out to assess the presence of some pesticides (diafenthiuron, lufenuron, azoxystrobin, difenoconazole, and chlorothalonil) residues in five of the very commonly used vegetables (eggplant, capsicum, apple gourd, cauliflower, and sponge gourd). Matrix solid phase dispersion (MSPD) technique was used to extract the pesticides and subsequently their quantification was performed through high performance liquid chromatography (HPLC) coupled to ultraviolet-visible (UV-Vis) detector. The elution was accomplished at wavelength of 254 nm by injecting 20 µL of standards or samples into chromatographic system. The mobile phase consisted of acetonitrile and water (80:20 v/v), where the flow rate was adjusted at 1.0 ml/min. The linearity was good (R2 ≥ 0.994) over a concentration range from 20 to 100 μg/ml for the investigated pesticides. The low detection limits showed a quite appreciable potential of the method to detect (1.12–1.61 μg/L) and quantify (3.73–5.36 μg/ml) the pesticides under study. The accuracy was demonstrated in terms of percent recovery which ranged between 88.5% and 116.9% for all the pesticides under investigation. These results justify the suitability of the technique for the intended purpose. The concentration of difenoconazole in apple gourd (20.97 mg/kg), cauliflower (10.28 mg/kg), and sponge gourd (40.32 mg/kg) whereas diafenthiuron in cauliflower (0.66 mg/kg) exceeded the maximum residue level (MRLs) as defined by Food and Agriculture Organization of the United Nations and the World Health Organization (FAO/WHO). Target hazard quotient (THQ) values of difenoconazole and diafenthiuron (except for adults) were more than one which indicates the significant effect on human health on consumption of apple gourd, cauliflower, and sponge gourd.

Phosphonates and bisphosphonates are stable analogs of phosphates and pyrophosphates that are characterized by one and two carbon–phosphorus bonds, respectively. Among the various phosphonates and bisphosphonates, hydroxy and amino substitutes are of interest as effective in medicinal and industrial chemistry. For example, hydroxy bisphosphonates have proven to be effective for the prevention of bone loss, especially in osteoporotic disease. On the other hand, different substitutions on the carbon atom connected to phosphorus have led to the synthesis of many different hydroxy- and amino-phosphonates and -bisphosphonates, each with its distinct physical, chemical, biological, therapeutic, and toxicological characteristics. Dialkyl or aryl esters of phosphonate and bisphosphonate compounds undergo the hydrolysis process readily and gave valuable materials with wide applications in pharmaceutical and agriculture. This review aims to demonstrate the ongoing preparation of various classes of hydroxy- and amino-phosphonates and -bisphosphonates. Furthermore, the current review summarizes and comprehensively describes articles on the biological applications of hydroxyl- and amino-phosphonates and -bisphosphonates from 2015 until today.

Pesticide residues, when present in agricultural wastewater, constitute a potential risk for the environment and human health. Hence, focused actions for their abatement are of high priority for both the industrial sectors and national authorities. This work evaluates the effectiveness of the photocatalytic process to decompose two frequently detected pesticides in the water effluents of the fruit industry: thiamethoxam-a neonicotinoid compound and flonicamid-a pyridine derivative. Their photocatalytic degradation and mineralization were evaluated in a lab-scale photocatalytic batch reactor under UV-A illumination with the commercial photocatalyst Evonik P25 TiO2 by employing different experimental conditions. The complete degradation of thiamethoxam was achieved after 90 min, when the medium was adjusted to natural or alkaline pH. Flonicamid was proven to be a more recalcitrant substance and the removal efficiency reached ~50% at the same conditions, although the degradation overpassed 75% in the acidic pH medium. Overall, the pesticides’ degradation follows the photocatalytic reduction pathways, where positive charged holes and hydroxyl radicals dominate as reactive species, with complete mineralization taking place after 4 h, regardless of the pH medium. Moreover, it was deduced that the pesticides’ degradation kinetics followed the Langmuir-Hinshelwood (L-H) model, and the apparent rate constant, the initial degradation rate, as well as the L-H model parameters, were determined for both pesticides.

Pyrethroids are insecticides most commonly used for insect control to boost agricultural production. The aim of the present research was to determine the effect of permethrin and cypermethrin on cultured and non-cultivated bacteria and fungi and on the activity of soil enzymes, as well as to determine the usefulness of Zea mays in mitigating the adverse effects of the tested pyrethroids on the soil microbiome. The analyses were carried out in the samples of both soil not sown with any plant and soil sown with Zea mays. Permethrin and cypermethrin were found to stimulate the multiplication of cultured organotrophic bacteria (on average by 38.3%) and actinomycetes (on average by 80.2%), and to inhibit fungi growth (on average by 31.7%) and the enzymatic activity of the soil, reducing the soil biochemical fertility index (BA) by 27.7%. They also modified the number of operational taxonomic units (OTUs) of the Actinobacteria and Proteobacteria phyla and the Ascomycota and Basidiomycota phyla. The pressure of permethrin and cypermethrin was tolerated well by the bacteria Sphingomonas (clone 3214512, 1052559, 237613, 1048605) and Bacillus (clone New.ReferenceOTU111, 593219, 578257), and by the fungi Penicillium (SH1533734.08FU, SH1692798.08FU) and Trichocladium (SH1615601.08FU). Both insecticides disturbed the growth and yielding of Zea mays, as a result of which its yield and leaf greenness index decreased. The cultivation of Zea mays had a positive effect on both soil enzymes and soil microorganisms and mitigated the anomalies caused by the tested insecticides in the microbiome and activity of soil enzymes. Permethrin decreased the yield of its aerial parts by 37.9% and its roots by 33.9%, whereas respective decreases caused by cypermethrin reached 16.8% and 4.3%.

Natural products constitute an important source of molecules for product development. However, despite numerous reports of compounds and active extracts from biodiversity, poor and developing countries continue to suffer with endemic diseases caused by arboviral vectors, including dengue, Zika, chikungunya and urban yellow fever. Vector control remains the most efficient disease prevention strategy. Wide and prolonged use of insecticides has resulted in vector resistance, making the search for new chemical prototypes imperative. Considering the potential of natural products chemistry for developing natural products-based products, including insecticides, this contribution discusses the general aspects and specific characteristics involved in the development of drug leads for vector control. Throughout this work, we highlight the obstacles that need to be overcome in order for natural products compounds to be considered promising prototypes. Moreover, we analyze the bottlenecks that should be addressed, together with potential strategies, to rationalize and improve the efficiency of the drug discovery process.

Eugenol, a natural phenolic allyl benzene that has been used as an active lead compound showing significant biological activities, including insecticidal effects on a wide variety of domestic arthropod pests, was used as the main reagent in the present work. Ester eugenol derivatives were synthesized and evaluated for their insecticidal activities against the Spodoptera frugiperda cell line. Studies of structure-based inverted virtual screening were carried out in order to identify the potential targets associated with the obtained insecticidal activity. The results indicate that the insecticide activity observed is most likely a result of the interaction of these molecules with the odorant-binding proteins and/or with acetylcholinesterase.

Aminobenzoic acid derivatives have shown various pharmacological properties, one of which is pesticide activity, giving these compounds the ability to work as alternatives to current pesticides. Nanotechnology could efficiently support the use of these compounds by encapsulating them in stable nanoformulations to improve their stability and effectiveness. In the present work, 3-chloropropylaminobenzoate derivatives were synthesised and evaluated against their effect on the viability of the insect cell line Sf9 (Spodoptera frugiperda), and nanoencapsulation studies of the most active compound were carried out. The most potent molecules reduced insect cell viability by around 40% at 100 µg/mL.

A recently synthesized new eugenol derivative, ethyl 4-(2-methoxy-4-(oxiran-2-ylmethyl)phenoxy)butanoate, with a high insecticidal activity against Sf9 (Spodoptera frugiperda) insect cells, was encapsulated in the liposomal formulations of egg-phosphatidylcholine/cholesterol (Egg-PC:Ch) 70:30 and 100% dioleoylphosphatidylglycerol (DOPG), aiming at the future application as insecticides. Compound-loaded DOPG liposomes have sizes of 274 ± 12 nm, while Egg-PC:Ch liposomes exhibit smaller hydrodynamic diameters (69.5 ± 7 nm), high encapsulation efficiency (88.8 ± 2.7%), higher stability, and a more efficient compound release, thus, they were chosen for assays in Sf9 insect cells. The compound elicited a loss of cell viability up to 80% after 72 h of incubation. Relevantly, nanoencapsulation maintained the toxicity of the compound toward insect cells while lowering the toxicity toward human cells, thus showing the selectivity of the system. Structure-based inverted virtual screening was used to predict the most likely targets and molecular dynamics simulations and free energy calculations were used to demonstrate that this molecule can form a stable complex with insect odorant binding proteins and/or acetylcholinesterase. The results are promising for the future application of compound-loaded nanoliposome formulations as crop insecticides.

Insecticides and rodenticides form the basis of integrated pest management systems worldwide. As pest resistance continues to increase and entire groups of chemical active ingredients are restricted or banned, manufacturers are looking for new options for more effective formulations and safer application methods for the remaining pesticide ingredients. In addition to new technological adaptations of mainstream formulations in the form of sprays, fumigants, and dusts, the use of gel formulations is becoming increasingly explored and employed. This article summarizes information on the current and potential use of gel (including hydrogel) and paste formulations against harmful arthropods or rodents in specific branches of pest management in the agricultural, food, stored product, structural wood, urban, medical, and public health areas. Due to the worldwide high interest in natural substances, part of the review was devoted to the use of gels for the formulation of pesticide substances of botanical origin, such as essential or edible oils. Gels as emerging formulation of so called “smart insecticides” based on molecular iRNA disruptors are discussed.

Lipid nanoparticles (LN) composed of biodegradable lipids and produced by green methods are candidates for the encapsulation of pesticides, potentially contributing to decreasing their release in the environment. From a safety-by-design concept, this work proposes LN for the encapsulation of insecticide active ingredients (AI). However, given the complexity of nanoparticles, ecotoxicological studies are often controversial, and a detailed investigation of their effects on the environment is required. Accordingly, this work aimed to produce and characterize LN containing the insecticide lambda-cyhalothrin (LC) and evaluate their safety to crops (Solanum lycopersicum and Zea mays), soil invertebrates (Folsomia candida and Eisenia fetida), and soil microbial parameters. The average particle size for LN-loaded with LC (LN–LC) was 165.4 ± 2.34 nm, with narrow size distribution and negative charge (−38.7 ± 0.954 mV). LN were able to encapsulate LC with an entrapment efficacy of 98.44 ± 0.04%, maintaining the stability for at least 4 months. The LN–LC showed no risk to the growth of crops and reproduction of the invertebrates. The effect on microbial parameters showed that the activity of certain soil microbial parameters can be inhibited or stimulated by the presence of LN at highest concentrations, probably by changing the pH of soil or by the intrinsic properties of LN.

The article considers fipronil determination by the method of RP HPLC in isocratic mode with ultraviolet detection at 280 nm. The analysis of insecticidal gels containing fipronil and fipronil mixture with chlorpyriphos was carried out. The possibility and expediency of determining the isomeric composition of fipronil were considered. The conditions for carrying out extraction of insecticides from gel matrices containing food attractive, including additional processing by ultrasound, were determined. The developed mode of extraction of active ingredients (fipronil and chlorpyriphos) is based on the preferred homogenization of the gel sample with a minimum amount of water followed by extraction with isopropanol acidified with acetic acid. The proposed scheme differs from the previously realized chloroform extraction by the stage of sample preparation. However, under these conditions in case of the gel matrix it is possible to achieve a high degree of homogeneity of the sample and to prevent possible hydrolysis of the target components. At the same time, the selected conditions are well combined with the polarity of the mobile phase upon direct separation. Selected chromatography modes allow identifying the title compound in real insecticides without overlapping signals from other extractable components using the trivial stationary phases. The possibility and expediency of carrying out chromatographic analysis to determine the optical isomers of the title compounds with different insecticidal activity have been considered. The optimal concentration range of fipronil determination in the working solution is from 0.005 to 0.15 mg/ml (chlorpyriphos, from 0.002 to 0.15 mg/ml). The limit of determination of substance in the working solution/swabs is 0.0005 mg/ml.

In order to find alternative pesticides, a series of benzamide derivatives was synthesized. An in silico inverted virtual screening protocol considering the 13 common insecticide protein targets was used to evaluate the potential insecticide activity of these molecules and identify the most likely targets. The results suggest important clues for the development of this class of derivatives as alternative insecticides.

The synthesis of three alkoxy alcohols with different chains was carried out from eugenol oxirane. These derivatives were evaluated against their effect on the viability of the insect cell line Sf9 (Spodoptera frugiperda). The molecules under study displayed mild-cytotoxic activity towards insect cells, equivalent to the commercial insecticide chlorpyrifos. Nanoencapsulation studies of the most active compound against Sf9 were performed using liposomes of egg-phosphatidylcholine containing 30% cholesterol. The encapsulation efficiency is around 93%, and the release profile for 24 h follows a Korsmeyer–Peppas model.

Processes on wastewater treatment plants (WWTP) are not always efficient for pollutant removal. A new, low-cost, and effective technology is needed. In this work, the photocatalytic degradation of four insecticides, chlorantraniliprole, imidacloprid, pirimicarb, and thiamethoxam, has been examined in different water matrices (irrigation water, leaching waters, and WWTP effluent). Lab experiments were conducted with TiO2 and ZnO, as photocatalysts, with and without Na2S2O8 as an oxidant, exposed to UVA irradiation with LED lamps. Previously, different loadings of TiO2 and ZnO were assessed on the disappearance kinetics of the different insecticides to know the optimal efficiency. The effect of water matrices, susceptible to being contaminated with the target insecticides, was discussed when the photocatalytic system TiO2/Na2S2O8 was applied. The abatement of their main transformation products (TPs) was also monitored during the studied photoperiods. A total of 13 TPs were detected in the different water matrices studied. All of them were formed and eliminated during the photoperiod, except thiamethoxam urea which was present from the beginning of the experiments due to its hydrolysis in water. In conclusion, UVA-LED lamps are a good source to carry out heterogeneous photocatalysis in WWTP, since its high efficiency, low-cost, long lifetime, and effectiveness on pollutant removal.

The cabbage stem flea beetle (CSFB), Psylliodes chrysocephala (Coleoptera: Chrysomelidae), has recently become a major pest species in winter oilseed rape in the Czech Republic. The susceptibility of CSFB populations from two localities to six pyrethroids, two neonicotinoids, one organophosphate and one oxadiazine was evaluated in 2015–2018 in glass vial experiments. The susceptibility of CSFB to thiacloprid and thiamethoxam was evaluated in feeding experiment in 2017 and 2018. High susceptibility of CSFB populations to lambda-cyhalothrin, cypermethrin, esfenvalerate, tau-fluvalinate, etofenprox, deltamethrin, chlorpyrifos, indoxacarb and acetamiprid was observed in the glass vial experiments. The LC50 and LC90 data obtained for pyrethroids in these experiments in 2015 represent baseline for CSFB resistance monitoring to pyrethroids in the Czech Republic. High tolerance of CSFB to thiacloprid of CSFB was demonstrated in glass vial and the feeding experiment, too. [ABSTRACT FROM AUTHOR]

Dengue is one of the most serious mosquito-borne infectious diseases in the world. Aedes albopictus is the most invasive mosquito and one of the primary vectors of dengue. Vector control using insecticides is the only viable strategy to prevent dengue virus transmission. In Guangzhou, after the 2014 pandemic, massive insecticides have been implemented. Massive insecticide use may lead to the development of resistance, but few reports are available on the status of insecticide resistance in Guangzhou after 2014. In this study, Ae. albopictus were collected from four districts with varied dengue virus transmission intensity in Guangzhou from 2015 to 2017. Adult Ae. albopictus insecticide susceptibility to deltamethrin (0.03%), permethrin(0.25%), DDT(4%), malathion (0.8%) and bendiocarb (0.1%) was determined by the standard WHO tube test, and larval resistance bioassays were conducted using temephos, Bacillus thuringiensis israelensis (Bti), pyriproxyfen (PPF) and hexaflumuron. Mutations at the voltage-gated sodium channel (VGSC) gene and acetylcholinesterase (AChE) gene were analyzed. The effect of cytochrome P450s on the resistance of Ae. albopictus to deltamethrin was tested using the synergistic agent piperonyl butoxide (PBO). The results showed that Ae. albopictus populations have rapidly developed very high resistances to multiple commonly used insecticides at all study areas except malathion, Bti and hexaflumuron. We found 1534 codon mutations in the VGSC gene that were significantly correlated with the resistance to pyrethroids and DDT, and 11 synonymous mutations were also found in the gene. The resistance to deltamethrin can be significantly reduced by PBO but may generated cross-resistance to PPF. Fast emerging resistance in Ae. albopictus may affect mosquito management and threaten the prevention and control of dengue, similar to the resistance in Anopheles mosquitoes has prevented the elimination of malaria and call for timely and guided insecticide management. [ABSTRACT FROM AUTHOR]

Bees provide essential ecosystem services and help maintain floral biodiversity. However, there is an ongoing decline of wild and domesticated bee species. Since agricultural pesticide use is a key driver of this process, there is a need for a protective risk assessment. To achieve a more protective registration process, two bee species, Osmia bicornis/Osmia cornuta and Bombus terrestris, were proposed by the European Food Safety Authority as additional test surrogates to the honey bee Apis mellifera. We investigated the acute toxicity (median lethal dose, LD50) of multiple commercial insecticide formulations towards the red mason bee (O. bicornis) and compared these values to honey bee regulatory endpoints. In two thirds of all cases, O. bicornis was less sensitive than the honey bee. By applying an assessment factor of 10 on the honey bee endpoint, a protective level was achieved for 87% (13 out 15) of all evaluated products. Our results show that O. bicornis is rarely an adequate additional surrogate species for lower tier risk assessment since it is less sensitive than the honey bee for the majority of investigated products. Given the currently limited database on bee species sensitivity, the honey bee seems sufficiently protective in acute scenarios as long as a reasonable assessment factor is applied. However, additional surrogate species can still be relevant for ecologically meaningful higher tier studies. [ABSTRACT FROM AUTHOR]

Resistance to insecticides can hamper the control of mosquitoes such as Culex quinquefasciatus, known to vector arboviruses such as West Nile virus and others. The strong selective pressure exerted on a mosquito population by the use of insecticides can result in heritable genetic changes associated with resistance. We sought to characterize genetic differences between insecticide resistant and susceptible Culex quinquefasciatus mosquitoes using targeted DNA sequencing. To that end, we developed a panel of 122 genes known or hypothesized to be involved in insecticide resistance, and used an Ion Torrent PGM sequencer to sequence 125 unrelated individuals from seven populations in the southern U.S. whose resistance phenotypes to permethrin and malathion were known from previous CDC bottle bioassay testing. Data analysis consisted of discovering SNPs (Single Nucleotide Polymorphism) and genes with evidence of copy number variants (CNVs) statistically associated with resistance. Ten of the seventeen genes found to be present in higher copy numbers were experimentally validated with real-time PCR. Of those, six, including the gene with the knock-down resistance (kdr) mutation, showed evidence of a ≥ 1.5 fold increase compared to control DNA. The SNP analysis revealed 228 unique SNPs that had significant p-values for both a Fisher’s Exact Test and the Cochran-Armitage Test for Trend. We calculated the population frequency for each of the 64 nonsynonymous SNPs in this group. Several genes not previously well characterized represent potential candidates for diagnostic assays when further validation is conducted. [ABSTRACT FROM AUTHOR]